Oncogenes

The first clues that cancer has a genetic basis came from several independent observations. In 1914 the German cell biologist Theodor Boveri viewed cancer cells through a microscope and noted that they often carried abnormal chromosomes. However, recognition that a specific chromosomal abnormality was routinely associated with a particular type of cancer did not come until 1973, when Janet Rowley showed that chronic myelogenous leukemia (CML) cells carried a chromosomal translocation in which the ends of chromosomes nine and twenty-two are exchanged. Several other studies showed that certain types of cancer can run in families, suggesting that cancer risk can be inherited. Then, in 1981 the laboratories of Robert Weinberg, Michael Wigler, Geoff Cooper, and Mariano Barbacid showed that DNA from a human bladder cancer cell line could cause nonmalignant cells in tissue culture to become cancerous.

Since the Weinberg and Wigler observations, dozens of oncogenes have been identified and characterized. It is clear that oncogenes represent certain normal cellular genes that are aberrantly expressed or functionally abnormal. Such normal cellular genes, or "proto-oncogenes," can be altered to become oncogenes through a variety of different molecular mechanisms.